IGG FC Variants for Veterinary Use

Abstract

Provided are various embodiments relating to variant IgG Fc polypeptides of companion animals having increased Protein A binding for ease of purification, decreased C1q binding for reduced complement-mediated immune responses, decreased CD 16 binding (e.g., for reduced antibody-dependent cellular cytotoxicity (ADCC) induction), increased stability, and/or the ability to form multimeric proteins. In addition, various embodiments relating to antibodies and fusion proteins comprising such variant IgG Fc polypeptides are provided. In various embodiments, such polypeptides may be used to treat companion animals, such as canines, felines, and equines.

1 . A polypeptide comprising at least one therapeutic polypeptide and/or at least one antibody, and a variant IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises:
 a) at least one amino acid modification relative to a wild-type IgG Fc polypeptide of a companion animal species, wherein the variant IgG Fc polypeptide has increased binding affinity to Protein A relative to the wild-type IgG Fc polypeptide;   b) at least one amino acid modification relative to a wild-type IgG Fc polypeptide of a companion animal species, wherein the variant IgG Fc polypeptide has reduced binding affinity to C1q relative to the wild-type IgG Fc polypeptide;   c) at least one amino acid modification relative to a wild-type IgG Fc polypeptide of a companion animal species, wherein the variant IgG Fc polypeptide has reduced binding affinity to CD16 relative to the wild-type IgG Fc polypeptide;   d) a hinge region comprising at least one amino acid modification to relative to a wild-type feline or equine IgG Fc polypeptide, wherein the variant IgG Fc polypeptide has increased recombinant production and/or increased hinge disulfide formation relative to the wild-type IgG Fc polypeptide, as determined by SDS-PAGE analysis under reducing and/or nonreducing conditions;   e) at least one amino acid substitution relative to a wild-type feline IgG Fc polypeptide, wherein the at least one amino acid substitution is a cysteine, and wherein the variant IgG Fc polypeptide is capable of forming at least one additional inter-chain disulfide linkage relative to the wild-type feline IgG Fc polypeptide;   f) at least one amino acid substitution relative to a wild-type canine IgG-A or IgG-D Fc polypeptide, wherein the variant IgG Fc polypeptide has increased binding affinity to C1q and/or CD16 relative to the wild-type canine IgG-A or IgG-D Fc polypeptide; and/or   g) a CH1 region comprising at least one amino acid modification relative to a wild-type canine or feline IgG CH1 region, wherein the variant IgG Fc polypeptide comprises:
 i) at least one amino acid substitution at a position corresponding to position 24 and/or position 30 of SEQ ID NO: 142, of SEQ ID NO: 143, of SEQ ID NO: 144, or of SEQ ID NO: 145, or 
 ii) at least one amino acid substitution at a position corresponding to position 24 and/or position 29 of SEQ ID NO: 152 or of SEQ ID NO: 153. 
   
     
     
         2 . A contiguous polypeptide comprising:
 i) a first therapeutic polypeptide and/or antibody (TPA1);   ii) a first linker (L1);   iii) a variant Fc polypeptide (Fc) of a companion animal species;   iv) optionally, a second linker (L2); and   v) optionally, a second therapeutic polypeptide and/or antibody (TPA2),   
       wherein the variant IgG Fc polypeptide comprises:
 a) at least one amino acid modification relative to a wild-type IgG Fc polypeptide of a companion animal species, wherein the variant IgG Fc polypeptide has increased binding affinity to Protein A relative to the wild-type IgG Fc polypeptide; 
 b) at least one amino acid modification relative to a wild-type IgG Fc polypeptide of a companion animal species, wherein the variant IgG Fc polypeptide has reduced binding affinity to C1q relative to the wild-type IgG Fc polypeptide; 
 c) at least one amino acid modification relative to a wild-type IgG Fc polypeptide of a companion animal species, wherein the variant IgG Fc polypeptide has reduced binding affinity to CD16 relative to the wild-type IgG Fc polypeptide; 
 d) a hinge region comprising at least one amino acid modification to relative to a wild-type feline or equine IgG Fc polypeptide, wherein the variant IgG Fc polypeptide has increased recombinant production and/or increased hinge disulfide formation relative to the wild-type IgG Fc polypeptide, as determined by SDS-PAGE analysis under reducing and/or nonreducing conditions; and/or 
 e) at least one amino acid substitution relative to a wild-type feline IgG Fc polypeptide, wherein the at least one amino acid substitution is a cysteine, and wherein the variant IgG Fc polypeptide is capable of forming at least one additional inter-chain disulfide linkage relative to the wild-type feline IgG Fc polypeptide; 
 f) at least one amino acid substitution relative to a wild-type canine IgG-A or IgG-D Fc polypeptide, wherein the variant IgG Fc polypeptide has increased binding affinity to C1q and/or CD16 relative to the wild-type canine IgG-A or IgG-D Fc polypeptide; and/or 
 g) a CH1 region comprising at least one amino acid modification relative to a wild-type canine or feline IgG CH1 region, wherein the variant IgG Fc polypeptide comprises:
 i) at least one amino acid substitution at a position corresponding to position 24 and/or position 30 of SEQ ID NO: 142, of SEQ ID NO: 143, of SEQ ID NO: 144, or of SEQ ID NO: 145, or 
 ii) at least one amino acid substitution at a position corresponding to position 24 and/or position 29 of SEQ ID NO: 152 or of SEQ ID NO: 153. 
 
 
     
     
         3 . The contiguous polypeptide of  claim 2  comprising:
   TPA1-L1-Fc  formula (I):
 
   Fc-L1-TPA1;  formula (II):
 
   TPA1-L1-Fc-L2-TPA2;  formula (III):
 
   TPA1-L1-TPA2-L2-Fc; or  formula (IV):
 
   Fc-L1-TPA1-L2-TPA2.  formula (V):
 
 
     
     
         4 . A multimeric protein comprising:
 i) a first therapeutic polypeptide and/or an antibody (TPA1), and a first variant IgG Fc polypeptide comprising at least one amino acid modification relative to a first wild-type IgG Fc polypeptide, and   ii) a second therapeutic polypeptide and/or an antibody (TPA2), and a second variant IgG Fc polypeptide comprising at least one amino acid modification relative to a second wild-type IgG Fc polypeptide, wherein
 a) the first variant IgG Fc polypeptide comprises:
 i) an amino acid substitution at a position corresponding to position 138 of SEQ ID NO: 1, position 137 of SEQ ID NO: 2, position 137 of SEQ ID NO: 4, or position 138 of SEQ ID NO: 6; 
 ii) an amino acid substitution at a position corresponding to position 154 of SEQ ID NO: 65, of SEQ ID NO: 66, of SEQ ID NO: 67, of SEQ ID NO: 68, or of SEQ ID NO: 69; or 
 iii) an amino acid substitution at a position corresponding to position 131 of SEQ ID NO: 49, of SEQ ID NO: 50, of SEQ ID NO: 52, of SEQ ID NO: 53, of SEQ ID NO: 54, of SEQ ID NO: 55, or of SEQ ID NO: 56; and 
 
 b) the second variant IgG Fc polypeptide comprises:
 i) an amino acid substitution at a position corresponding to position 138, position 140, and/or position 181 of SEQ ID NO: 1, position 137, position 139, and/or position 180 of SEQ ID NO: 2, position 137, position 139, and/or position 180 of SEQ ID NO: 3, or position 138, position 140, and/or position 181 of SEQ ID NO: 4; 
 ii) an amino acid substitution at a position corresponding to position 154, position 156, and/or position 197 of SEQ ID NO: 6, of SEQ ID NO: 80, of SEQ ID NO: 81, of SEQ ID NO: 117, or of SEQ ID NO: 118; or 
 iii) an amino acid substitution at a position corresponding to position 131, position 133, and/or position 174 of SEQ ID NO: 49, of SEQ ID NO: 50, of SEQ ID NO: 52, of SEQ ID NO: 53, of SEQ ID NO: 54, of SEQ ID NO: 55, or of SEQ ID NO: 56. 
 
   
     
     
         5 . The multimeric protein of  claim 4 , wherein the first variant IgG Fc polypeptide and/or the second variant IgG Fc polypeptide comprises:
 a) at least one amino acid modification relative to a wild-type IgG Fc polypeptide of a companion animal species, wherein the first and/or second variant IgG Fc polypeptide has increased binding affinity to Protein A relative to the wild-type IgG Fc polypeptide;   b) at least one amino acid modification relative to a wild-type IgG Fc polypeptide of a companion animal species, wherein the first and/or second variant IgG Fc polypeptide has reduced binding affinity to C1q relative to the wild-type IgG Fc polypeptide;   c) at least one amino acid modification relative to a wild-type IgG Fc polypeptide of a companion animal species, wherein the first and/or second variant IgG Fc polypeptide has reduced binding affinity to CD16 relative to the wild-type IgG Fc polypeptide;   d) a hinge region comprising at least one amino acid modification to relative to a wild-type feline or equine IgG Fc polypeptide, wherein the first and/or second variant IgG Fc polypeptide has increased recombinant production and/or increased hinge disulfide formation relative to the wild-type IgG Fc polypeptide, as determined by SDS-PAGE analysis under reducing and/or nonreducing conditions;   e) at least one amino acid substitution relative to a wild-type feline IgG Fc polypeptide, wherein the at least one amino acid substitution is a cysteine, and wherein the first and/or second variant IgG Fc polypeptide is capable of forming at least one additional inter-chain disulfide linkage relative to the wild-type feline IgG Fc polypeptide; and/or   f) at least one amino acid substitution relative to a wild-type canine IgG-A or IgG-D Fc polypeptide, wherein the variant IgG Fc polypeptide has increased binding affinity to C1q and/or CD16 relative to the wild-type canine IgG-A or IgG-D Fc polypeptide; and/or   g) a CH1 region comprising at least one amino acid modification relative to a wild-type canine or feline IgG CH1 region, wherein the variant IgG Fc polypeptide comprises:
 i) at least one amino acid substitution at a position corresponding to position 24 and/or position 30 of SEQ ID NO: 142, of SEQ ID NO: 143, of SEQ ID NO: 144, or of SEQ ID NO: 145, or 
 ii) at least one amino acid substitution at a position corresponding to position 24 and/or position 29 of SEQ ID NO: 152 or of SEQ ID NO: 153. 
   
     
     
         6 . The multimeric protein of  claim 4  or  claim 5 , wherein the first wild-type IgG Fc polypeptide and the second wild-type IgG Fc polypeptide are from the same IgG subtype. 
     
     
         7 . The multimeric protein of  claim 4  or  claim 5 , wherein the first wild-type IgG Fc polypeptide and the second wild-type IgG Fc polypeptide are from a different IgG subtype. 
     
     
         8 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of  claims 2  to  7 , wherein TPA2, if present, comprises a different amino acid sequence compared to TPA1. 
     
     
         9 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of  claims 2  to  8 , wherein TPA1 and TPA2 are different therapeutic polypeptides or are antibodies that bind to different targets. 
     
     
         10 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide binds to C1q and/or CD16 with a dissociation constant (K d ) of greater than 5×10 −6  M, greater than 1×10 −5  M, greater than 5×10 −5 M, greater than 1×10 −4  M, greater than 5×10 −4  M, or greater than 1×10 −3 M, as measured by biolayer interferometry. 
     
     
         11 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide binds to Protein A with a dissociation constant (K d ) of less than 5×10 −6  M, less than 1×10 −6  M, less than 5×10 −7 M, less than 1×10 −7  M, less than 5×10 −8 M, less than 1×10 −8  M, less than 5×10 −9 M, less than 1×10 −9 M, less than 5×10 −10  M, less than 1×10 −10  M, less than 5×10 −11 M, less than 1×10 −11 M, less than 5×10 −12  M, or less than 1×10 −12 M, as measured by biolayer interferometry. 
     
     
         12 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant canine IgG-A or variant canine IgG-D Fc polypeptide binds to C1q and/or CD16 with a dissociation constant (K d ) of less than 5×10 −6  M, less than 1×10 −6  M, less than 5×10 −7 M, less than 1×10 −7 M, less than 5×10 −8  M, less than 1×10 −8  M, less than 5×10 −9 M, less than 1×10 −9  M, less than 5×10 −10  M, less than 1×10 −10  M, less than 5×10 −11 M, less than 1×10 −11 M, less than 5×10 −12 M, or less than 1×10 −12 M, as measured by biolayer interferometry. 
     
     
         13 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the companion animal species is canine, feline, or equine. 
     
     
         14 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the wild-type IgG Fc polypeptide is
 a) a canine IgG-A Fc, IgG-B Fc, IgG-C Fc, or IgG-D Fc;   b) an equine IgG1 Fc, IgG2 Fc, IgG3 Fc, IgG4 Fc, IgG5 Fc, IgG6 Fc, or IgG7 Fc; or   c) a feline IgG1a Fc, IgG1b Fc, or IgG2 Fc.   
     
     
         15 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises a CH1 region comprising at least one amino acid modification relative to a wild-type canine or feline IgG CH1 region, wherein the variant IgG Fc polypeptide comprises:
 a) at least one amino acid substitution at position 24 and/or position 30 of SEQ ID NO: 142, of SEQ ID NO: 143, of SEQ ID NO: 144; or of SEQ ID NO: 145, or   b) at least one amino acid substitution at position 24 and/or position 29 of SEQ ID NO: 152 or of SEQ ID NO: 153.   
     
     
         16 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises a CH1 region comprising at least one amino acid modification relative to a wild-type canine or feline IgG CH1 region, wherein the variant IgG Fc polypeptide comprises:
 a) a leucine at a position corresponding to position 24 and/or an asparagine at a position corresponding to position 30 of SEQ ID NO: 142, of SEQ ID NO: 143, of SEQ ID NO: 144, or of SEQ ID NO: 145; or   b) a leucine at a position corresponding to position 24 and/or an asparagine at a position corresponding to position 29 of SEQ ID NO: 152 or of SEQ ID NO: 153.   
     
     
         17 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises a CH1 region comprising at least one amino acid modification relative to a wild-type canine or feline IgG CH1 region, wherein the variant IgG Fc polypeptide comprises:
 a) a leucine at position 24 and/or an asparagine at position 30 of SEQ ID NO: 142, of SEQ ID NO: 143, of SEQ ID NO: 144, or of SEQ ID NO: 145; or   b) a leucine at position 24 and/or an asparagine at position 29 of SEQ ID NO: 152 or of SEQ ID NO: 153.   
     
     
         18 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims comprising a wild-type or a variant canine or feline light chain constant region. 
     
     
         19 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims comprising a wild-type or a variant canine or feline light chain κ constant region. 
     
     
         20 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims comprising a variant light chain constant region comprising at least one amino acid modification relative to a wild-type canine or feline light chain κ constant region comprising:
 a) at least one amino acid substitution at a position corresponding to position 11 and/or position 22 of SEQ ID NO: 150; or 
 b) at least one amino acid substitution at a position corresponding to position 11 and/or position 22 of SEQ ID NO: 156. 
 
     
     
         21 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims comprising a variant light chain constant region comprising at least one amino acid modification relative to a wild-type canine or feline light chain κ constant region comprising:
 a) at least one amino acid substitution at a position corresponding to position 11 and/or position 22 of SEQ ID NO: 150; or 
 b) at least one amino acid substitution at a position corresponding to position 11 and/or position 22 of SEQ ID NO: 156. 
 
     
     
         22 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims comprising a variant light chain constant region comprising at least one amino acid modification relative to a wild-type canine or feline light chain κ constant region comprising:
 a) an alanine at a position corresponding to position 11 and/or an arginine at a position corresponding to position 22 of SEQ ID NO: 150; or 
 b) an alanine at a position corresponding to position 11 and/or an arginine at a position corresponding to position 22 of SEQ ID NO: 156. 
 
     
     
         23 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims comprising a variant light chain constant region comprising at least one amino acid modification relative to a wild-type canine or feline light chain κ constant region comprising:
 a) an alanine at position 11 and/or an arginine at position 22 of SEQ ID NO: 150; or 
 b) an alanine at position 11 and/or an arginine at position 22 of SEQ ID NO: 156. 
 
     
     
         24 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) at least one amino acid substitution relative to a wild-type feline IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises an amino acid substitution at a position corresponding to position 16 of SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, or SEQ ID NO: 69;   b) at least one amino acid substitution relative to a wild-type equine IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises an amino acid substitution at a position corresponding to position 3 of SEQ ID NO: 51; and/or   c) at least one amino acid substitution relative to a wild-type equine IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises an amino acid substitution at a position corresponding to position 20 of SEQ ID NO: 51.   
     
     
         25 . A polypeptide comprising a variant IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises:
 a) at least one amino acid substitution relative to a wild-type feline IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises an amino acid substitution at a position corresponding to position 16 of SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, or SEQ ID NO: 69;   b) at least one amino acid substitution relative to a wild-type equine IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises an amino acid substitution at a position corresponding to position 3 of SEQ ID NO: 51; and/or   c) at least one amino acid substitution relative to a wild-type equine IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises an amino acid substitution at a position corresponding to position 20 of SEQ ID NO: 51.   
     
     
         26 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) at least one amino acid substitution relative to a wild-type feline IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises an amino acid substitution at position 16 of SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, or SEQ ID NO: 69;   b) at least one amino acid substitution relative to a wild-type equine IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises an amino acid substitution at position 3 of SEQ ID NO: 51; and/or   c) at least one amino acid substitution relative to a wild-type equine IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises an amino acid substitution at position 20 of SEQ ID NO: 51.   
     
     
         27 . The polypeptide, the contiguous polypeptide, or the multimeric protein, wherein the variant IgG Fc polypeptide comprises:
 a) at least one amino acid substitution relative to a wild-type feline IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises a proline at a position corresponding to position 16 or at position 16 of SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, or SEQ ID NO: 69;   b) at least one amino acid substitution relative to a wild-type equine IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises a serine at a position corresponding to position 3 or at position 3 of SEQ ID NO: 51; and/or   c) at least one amino acid substitution relative to a wild-type equine IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises a proline at a position corresponding to position 20 or at position 20 of SEQ ID NO: 51.   
     
     
         28 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one the preceding claims, wherein the variant IgG Fc polypeptide comprises a hinge region or a portion of a hinge region from an IgG Fc polypeptide of a different isotype. 
     
     
         29 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises a hinge region or a portion of a hinge region from a wild-type feline IgG-1 Fc polypeptide or from a wild-type equine IgG1 Fc polypeptide. 
     
     
         30 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises a cysteine at a position corresponding to position 8, position 9, position 10, position 11, position 12, position 13, position 14, position 15, or position 16 of SEQ ID NO: 69. 
     
     
         31 . A polypeptide comprising a variant IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises a cysteine at a position corresponding to position 8, position 9, position 10, position 11, position 12, position 13, position 14, position 15, or position 16 of SEQ ID NO: 69. 
     
     
         32 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises a cysteine at a position corresponding to position 14 of SEQ ID NO: 69. 
     
     
         33 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises a cysteine at position 14 of SEQ ID NO: 69. 
     
     
         34 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) an amino acid substitution at a position corresponding to position 21 of SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 23 of SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 25 of SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 80 of SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 205 of SEQ ID NO: 1, and/or an amino acid substitution at a position corresponding to position 207 of SEQ ID NO: 1;   b) an amino acid substitution at a position corresponding to position 21 of SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 23 of SEQ ID NO: 4, and/or an amino acid substitution at a position corresponding to position 24 of SEQ ID NO: 4;   c) an amino acid substitution at a position corresponding to position 21 of SEQ ID NO: 6, an amino acid substitution at a position corresponding to position 23 of SEQ ID NO: 6, an amino acid substitution at a position corresponding to position 25 of SEQ ID NO: 6, an amino acid substitution at a position corresponding to position 80 of SEQ ID NO: 6, and/or an amino acid substitution at a position corresponding to position 207 of SEQ ID NO: 6;   d) an amino acid substitution at a position corresponding to position 15 of SEQ ID NO: 50, and/or an amino acid substitution at a position corresponding to position 203 of SEQ ID NO: 50;   e) an amino acid substitution at a position corresponding to position 199 of SEQ ID NO: 54, and/or an amino acid substitution at a position corresponding to position 200 of SEQ ID NO: 54; and/or   f) an amino acid substitution at a position corresponding to position 199 of SEQ ID NO: 55, an amino acid substitution at a position corresponding to position 200 of SEQ ID NO: 55, an amino acid substitution at a position corresponding to position 201 of SEQ ID NO: 55, and/or an amino acid substitution at a position corresponding to position 202 of SEQ ID NO: 55.   
     
     
         35 . A polypeptide comprising a variant IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises:
 a) an amino acid substitution at a position corresponding to position 21 of SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 23 of SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 25 of SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 80 of SEQ ID NO: 1, an amino acid substitution at a position corresponding to position 205 of SEQ ID NO: 1, and/or an amino acid substitution at a position corresponding to position 207 of SEQ ID NO: 1;   b) an amino acid substitution at a position corresponding to position 21 of SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 23 of SEQ ID NO: 4, and/or an amino acid substitution at a position corresponding to position 24 of SEQ ID NO: 4;   c) an amino acid substitution at a position corresponding to position 21 of SEQ ID NO: 6, an amino acid substitution at a position corresponding to position 23 of SEQ ID NO: 6, an amino acid substitution at a position corresponding to position 25 of SEQ ID NO: 6, an amino acid substitution at a position corresponding to position 80 of SEQ ID NO: 6, and/or an amino acid substitution at a position corresponding to position 207 of SEQ ID NO: 6;   d) an amino acid substitution at a position corresponding to position 15 of SEQ ID NO: 50, and/or an amino acid substitution at a position corresponding to position 203 of SEQ ID NO: 50;   e) an amino acid substitution at a position corresponding to position 199 of SEQ ID NO: 54, and/or an amino acid substitution at a position corresponding to position 200 of SEQ ID NO: 54; and/or   f) an amino acid substitution at a position corresponding to position 199 of SEQ ID NO: 55, an amino acid substitution at a position corresponding to position 200 of SEQ ID NO: 55, an amino acid substitution at a position corresponding to position 201 of SEQ ID NO: 55, and/or an amino acid substitution at a position corresponding to position 202 of SEQ ID NO: 55.   
     
     
         36 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) an amino acid substitution at position 21 of SEQ ID NO: 1, an amino acid substitution at position 23 of SEQ ID NO: 1, an amino acid substitution at position 25 of SEQ ID NO: 1, an amino acid substitution at position 80 of SEQ ID NO: 1, an amino acid substitution at position 205 of SEQ ID NO: 1, and/or an amino acid substitution at position 207 of SEQ ID NO: 1;   b) an amino acid substitution at position 21 of SEQ ID NO: 4, an amino acid substitution at position 23 of SEQ ID NO: 4, and/or an amino acid substitution at position 24 of SEQ ID NO: 4;   c) an amino acid substitution at position 21 of SEQ ID NO: 4, an amino acid substitution at position 23 of SEQ ID NO: 6, an amino acid substitution at position 25 of SEQ ID NO: 6, an amino acid substitution at position 80 of SEQ ID NO: 6, and/or an amino acid substitution at position 207 of SEQ ID NO: 6;   d) an amino acid substitution at position 15 of SEQ ID NO: 50, and/or an amino acid substitution at position 203 of SEQ ID NO: 50;   e) an amino acid substitution at position 199 of SEQ ID NO: 54, and/or an amino acid substitution at position 200 of SEQ ID NO: 54; and/or   f) an amino acid substitution at position 199 of SEQ ID NO: 55, an amino acid substitution at position 200 of SEQ ID NO: 55, an amino acid substitution at position 201 of SEQ ID NO: 55, and/or an amino acid substitution at position 202 of SEQ ID NO: 55.   
     
     
         37 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) a threonine at a position corresponding to position 21 of SEQ ID NO: 1, a leucine at a position corresponding to position 23 of SEQ ID NO: 1, an alanine at a position corresponding to position 25 of SEQ ID NO: 1, a glycine at a position corresponding to position 80 of SEQ ID NO: 1, an alanine at a position corresponding to position 205 of SEQ ID NO: 1, and/or a histidine at a position corresponding to position 207 of SEQ ID NO: 1;   b) a threonine at a position corresponding to position 21 of SEQ ID NO: 4, a leucine at a position corresponding to position 23 of SEQ ID NO: 4, and/or an isoleucine at a position corresponding to position 24 of SEQ ID NO: 4;   c) a threonine at a position corresponding to position 21 of SEQ ID NO: 6, a leucine at a position corresponding to position 23 of SEQ ID NO: 6, an alanine at a position corresponding to position 25 of SEQ ID NO: 6, a glycine at a position corresponding to position 80 of SEQ ID NO:6, and/or a histidine at a position corresponding to position 207 of SEQ ID NO: 6;   d) a threonine or a valine at a position corresponding to position 15 of SEQ ID NO: 50, and/or a tyrosine or a valine at a position corresponding to position 203 of SEQ ID NO: 50;   e) a leucine at a position corresponding to position 199 of SEQ ID NO: 54, and/or a histidine at a position corresponding to position 200 of SEQ ID NO: 54; and/or   f) a leucine at a position corresponding to position 199 of SEQ ID NO: 55, a histidine at a position corresponding to position 200 of SEQ ID NO: 55, an asparagine at a position corresponding to position 201 of SEQ ID NO: 55, and/or a histidine at a position corresponding to position 202 of SEQ ID NO: 55.   
     
     
         38 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) a threonine at position 21 of SEQ ID NO: 1, a leucine at position 23 of SEQ ID NO: 1, an alanine at position 25 of SEQ ID NO: 1, a glycine at position 80 of SEQ ID NO: 1, an alanine at position 205 of SEQ ID NO: 1, and/or a histidine at position 207 of SEQ ID NO: 1;   b) a threonine at position 21 of SEQ ID NO: 3, a leucine at position 23 of SEQ ID NO: 4, and/or an isoleucine at position 24 of SEQ ID NO: 4;   c) a threonine at a position 21 of SEQ ID NO: 6, a leucine at position 23 of SEQ ID NO: 6, an alanine at position 25 of SEQ ID NO: 6, a glycine at position 80 of SEQ ID NO: 6, and/or a histidine at position 207 of SEQ ID NO: 6;   d) a threonine or a valine at position 15 of SEQ ID NO: 50, and/or a tyrosine or a valine at position 203 of SEQ ID NO: 50;   e) a leucine at position 199 of SEQ ID NO: 54, and/or a histidine at position 200 of SEQ ID NO: 54; and/or   f) a leucine at position 199 of SEQ ID NO: 55, a histidine at position 200 of SEQ ID NO: 55, an asparagine at position 201 of SEQ ID NO: 55, and/or a histidine at position 202 of SEQ ID NO: 55.   
     
     
         39 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) an amino acid substitution at a position corresponding to position 93 of SEQ ID NO: 2, or an amino acid substitution at a position corresponding to position 93 of SEQ ID NO: 4;   b) an amino acid substitution at a position corresponding to position 87 of SEQ ID NO: 49, an amino acid substitution at a position corresponding to position 87 of SEQ ID NO: 52, an amino acid substitution at a position corresponding to position 87 of SEQ ID NO: 53, or an amino acid substitution at a position corresponding to position 87 of SEQ ID NO: 56; or   c) an amino acid substitution at a position corresponding to position 198 of SEQ ID NO: 65, an amino acid substitution at a position corresponding to position 198 of SEQ ID NO: 66, an amino acid substitution at a position corresponding to position 198 of SEQ ID NO: 67, or an amino acid substitution at a position corresponding to position 198 of SEQ ID NO: 68.   
     
     
         40 . A polypeptide comprising a variant IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises:
 a) an amino acid substitution at a position corresponding to position 93 of SEQ ID NO: 2, or an amino acid substitution at a position corresponding to position 93 of SEQ ID NO: 4;   b) an amino acid substitution at a position corresponding to position 87 of SEQ ID NO: 49, an amino acid substitution at a position corresponding to position 87 of SEQ ID NO: 52, an amino acid substitution at a position corresponding to position 87 of SEQ ID NO: 53, or an amino acid substitution at a position corresponding to position 87 of SEQ ID NO: 56; or   c) an amino acid substitution at a position corresponding to position 198 of SEQ ID NO: 65, an amino acid substitution at a position corresponding to position 198 of SEQ ID NO: 66, an amino acid substitution at a position corresponding to position 198 of SEQ ID NO: 67, or an amino acid substitution at a position corresponding to position 198 of SEQ ID NO: 68.   
     
     
         41 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) an amino acid substitution at position 93 of SEQ ID NO: 2, or an amino acid substitution at position 93 of SEQ ID NO: 4;   b) an amino acid substitution at position 87 of SEQ ID NO: 49, an amino acid substitution at position 87 of SEQ ID NO: 52, an amino acid substitution at position 87 of SEQ ID NO: 53, or an amino acid substitution at position 87 of SEQ ID NO: 56; or   c) an amino acid substitution at position 198 of SEQ ID NO: 65, an amino acid substitution at position 198 of SEQ ID NO: 66, an amino acid substitution at position 198 of SEQ ID NO: 67, or an amino acid substitution at position 198 of SEQ ID NO: 68.   
     
     
         42 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) an arginine at a position corresponding to position 93 of SEQ ID NO: 2, or an arginine at a position corresponding to position 93 of SEQ ID NO: 4;   b) a serine at a position corresponding to position 87 of SEQ ID NO: 49, a serine substitution at a position corresponding to position 87 of SEQ ID NO: 52, a serine at a position corresponding to position 87 of SEQ ID NO: 53, or a serine at a position corresponding to position 87 of SEQ ID NO: 56; or   c) an alanine at a position corresponding to position 198 of SEQ ID NO: 65, an alanine at a position corresponding to position 198 of SEQ ID NO: 66, an alanine at a position corresponding to position 198 of SEQ ID NO: 67, or an alanine at a position corresponding to position 198 of SEQ ID NO: 68.   
     
     
         43 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) an arginine at position 93 of SEQ ID NO: 2, or an arginine at position 93 of SEQ ID NO: 4;   b) a serine at position 87 of SEQ ID NO: 49, a serine at position 87 of SEQ ID NO: 52, a serine at position 87 of SEQ ID NO: 53, or a serine at position 87 of SEQ ID NO: 56; or   c) an alanine at position 198 of SEQ ID NO: 65, an alanine at position 198 of SEQ ID NO: 66, an alanine at position 198 of SEQ ID NO: 67, or alanine at position 198 of SEQ ID NO: 68.   
     
     
         44 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) an amino acid substitution at a position corresponding to position 5 of SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 38 of SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 39 of SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 97 of SEQ ID NO: 2, and/or an amino acid substitution at a position corresponding to position 98 of SEQ ID NO: 2; or   b) an amino acid substitution at a position corresponding to position 5 of SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 38 of SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 39 of SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 97 of SEQ ID NO: 4, and/or an amino acid substitution at a position corresponding to position 98 of SEQ ID NO: 4.   
     
     
         45 . A polypeptide comprising a variant IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises:
 a) an amino acid substitution at a position corresponding to position 5 of SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 38 of SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 39 of SEQ ID NO: 2, an amino acid substitution at a position corresponding to position 97 of SEQ ID NO: 2, and/or an amino acid substitution at a position corresponding to position 98 of SEQ ID NO: 2; or   b) an amino acid substitution at a position corresponding to position 5 of SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 38 of SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 39 of SEQ ID NO: 4, an amino acid substitution at a position corresponding to position 97 of SEQ ID NO: 4, and/or an amino acid substitution at a position corresponding to position 98 of SEQ ID NO: 4.   
     
     
         46 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) an amino acid substitution at position 5 of SEQ ID NO: 2, an amino acid substitution at position 38 of SEQ ID NO: 2, an amino acid substitution at position 39 of SEQ ID NO: 2, an amino acid substitution at position 97 of SEQ ID NO: 2, and/or an amino acid substitution at position 98 of SEQ ID NO: 2; or   b) an amino acid substitution at position 5 of SEQ ID NO: 4, an amino acid substitution at position 38 of SEQ ID NO: 4, an amino acid substitution at position 39 of SEQ ID NO: 4, an amino acid substitution at position 97 of SEQ ID NO: 4, and/or an amino acid substitution at position 98 of SEQ ID NO: 4.   
     
     
         47 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) a proline at a position corresponding to position 5 of SEQ ID NO: 2, a glycine at a position corresponding to position 38 of SEQ ID NO: 2, an arginine at a position corresponding to position 39 of SEQ ID NO: 2, an isoleucine at a position corresponding to position 97 of SEQ ID NO: 2, and/or a glycine at a position corresponding to position 98 of SEQ ID NO: 2; or   b) a proline at a position corresponding to position 5 of SEQ ID NO: 4, a glycine at a position corresponding to position 38 of SEQ ID NO: 4, an arginine at a position corresponding to position 39 of SEQ ID NO: 4, an isoleucine at a position corresponding to position 97 of SEQ ID NO: 4, and/or a glycine at a position corresponding to position 98 of SEQ ID NO: 4.   
     
     
         48 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) a proline at position 5 of SEQ ID NO: 2, a glycine at position 38 of SEQ ID NO: 2, an arginine at position 39 of SEQ ID NO: 2, an isoleucine at position 97 of SEQ ID NO: 2, and/or a glycine at position 98 of SEQ ID NO: 2; or   b) a proline at position 5 of SEQ ID NO: 4, a glycine at position 38 of SEQ ID NO: 4, an arginine at position 39 of SEQ ID NO: 4, an isoleucine at position 97 of SEQ ID NO: 4, and/or a glycine at position 98 of SEQ ID NO: 4.   
     
     
         49 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims comprises:
 a) a variant canine IgG-A Fc polypeptide comprising an alanine at a position corresponding to position 2 of SEQ ID NO: 1, a methionine or a lysine at a position corresponding to position 5 of SEQ ID NO: 1, a threonine at a position corresponding to position 21 of SEQ ID NO: 1, a leucine at a position corresponding to position 23 of SEQ ID NO: 1, an alanine at a position corresponding to position 25 of SEQ ID NO: 1, a valine at a position corresponding to position 35 of SEQ ID NO: 1, an asparagine at a position corresponding to position 38 of SEQ ID NO: 1, a proline at a position corresponding to position 39 of SEQ ID NO: 1, a glutamic acid at a position corresponding to position 65 of SEQ ID NO: 1, a glycine at a position corresponding to position 80 of SEQ ID NO: 1, a lysine at a position corresponding to position 93 of SEQ ID NO: 1, a asparagine at a position corresponding to position 96 of SEQ ID NO: 1, a lysine at a position corresponding to position 97 of SEQ ID NO: 1, an alanine at a position corresponding to position 98 of SEQ ID NO: 1, an alanine at a position corresponding to position 205 of SEQ ID NO: 1, and/or a histidine at a position corresponding to position 207 of SEQ ID NO: 1; or   b) a variant canine IgG-D Fc polypeptide comprising an alanine at a position corresponding to position 2 of SEQ ID NO: 6, a methionine or a lysine at a position corresponding to position 5 of SEQ ID NO: 6, a threonine at a position corresponding to position 21 of SEQ ID NO: 6, a leucine at a position corresponding to position 23 of SEQ ID NO: 6, an alanine at a position corresponding to position 25 of SEQ ID NO: 6, a valine at a position corresponding to position 35 of SEQ ID NO: 6, an asparagine at a position corresponding to position 38 of SEQ ID NO: 6, a proline at a position corresponding to position 39 of SEQ ID NO: 6, a glutamic acid at a position corresponding to position 65 of SEQ ID NO: 6, a glycine at a position corresponding to position 80 of SEQ ID NO: 6, a lysine at a position corresponding to position 93 of SEQ ID NO: 6, a asparagine at a position corresponding to position 96 of SEQ ID NO: 6, a lysine at a position corresponding to position 97 of SEQ ID NO: 6, an alanine at a position corresponding to position 98 of SEQ ID NO: 6, and/or a histidine at a position corresponding to position 207 of SEQ ID NO: 6.   
     
     
         50 . A polypeptide comprising:
 a) a variant canine IgG-A Fc polypeptide comprising an alanine at a position corresponding to position 2 of SEQ ID NO: 1, a methionine or a lysine at a position corresponding to position 5 of SEQ ID NO: 1, a threonine at a position corresponding to position 21 of SEQ ID NO: 1, a leucine at a position corresponding to position 23 of SEQ ID NO: 1, an alanine at a position corresponding to position 25 of SEQ ID NO: 1, a valine at a position corresponding to position 35 of SEQ ID NO: 1, an asparagine at a position corresponding to position 38 of SEQ ID NO: 1, a proline at a position corresponding to position 39 of SEQ ID NO: 1, a glutamic acid at a position corresponding to position 65 of SEQ ID NO: 1, a glycine at a position corresponding to position 80 of SEQ ID NO: 1, a lysine at a position corresponding to position 93 of SEQ ID NO: 1, a asparagine at a position corresponding to position 96 of SEQ ID NO: 1, a lysine at a position corresponding to position 97 of SEQ ID NO: 1, an alanine at a position corresponding to position 98 of SEQ ID NO: 1, an alanine at a position corresponding to position 205 of SEQ ID NO: 1, and/or a histidine at a position corresponding to position 207 of SEQ ID NO: 1; or   b) a variant canine IgG-D Fc polypeptide comprising an alanine at a position corresponding to position 2 of SEQ ID NO: 6, a methionine or a lysine at a position corresponding to position 5 of SEQ ID NO: 6, a threonine at a position corresponding to position 21 of SEQ ID NO: 6, a leucine at a position corresponding to position 23 of SEQ ID NO: 6, an alanine at a position corresponding to position 25 of SEQ ID NO: 6, a valine at a position corresponding to position 35 of SEQ ID NO: 6, an asparagine at a position corresponding to position 38 of SEQ ID NO: 6, a proline at a position corresponding to position 39 of SEQ ID NO: 6, a glutamic acid at a position corresponding to position 65 of SEQ ID NO: 6, a glycine at a position corresponding to position 80 of SEQ ID NO: 6, a lysine at a position corresponding to position 93 of SEQ ID NO: 6, a asparagine at a position corresponding to position 96 of SEQ ID NO: 6, a lysine at a position corresponding to position 97 of SEQ ID NO: 6, an alanine at a position corresponding to position 98 of SEQ ID NO: 6, and/or a histidine at a position corresponding to position 207 of SEQ ID NO: 6.   
     
     
         51 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims comprises:
 a) a variant canine IgG-A Fc polypeptide comprising an alanine at position 2 of SEQ ID NO: 1, a methionine or a lysine at position 5 of SEQ ID NO: 1, a threonine at position 21 of SEQ ID NO: 1, a leucine at position 23 of SEQ ID NO: 1, an alanine at position 25 of SEQ ID NO: 1, a valine at position 35 of SEQ ID NO: 1, an asparagine at position 38 of SEQ ID NO: 1, a proline at position 39 of SEQ ID NO: 1, a glutamic acid at position 65 of SEQ ID NO: 1, a glycine at position 80 of SEQ ID NO: 1, a lysine at position 93 of SEQ ID NO: 1, a asparagine at position 96 of SEQ ID NO: 1, a lysine at position 97 of SEQ ID NO: 1, an alanine at position 98 of SEQ ID NO: 1, an alanine at position 205 of SEQ ID NO: 1, and/or a histidine at position 207 of SEQ ID NO: 1; or   b) a variant canine IgG-D Fc polypeptide comprising an alanine at position 2 of SEQ ID NO: 6, a methionine or a lysine at position 5 of SEQ ID NO: 6, a threonine at position 21 of SEQ ID NO: 6, a leucine at position 23 of SEQ ID NO: 6, an alanine at position 25 of SEQ ID NO: 6, a valine at position 35 of SEQ ID NO: 6, an asparagine at position 38 of SEQ ID NO: 6, a proline at position 39 of SEQ ID NO: 6, a glutamic acid at position 65 of SEQ ID NO: 6, a glycine at position 80 of SEQ ID NO: 6, a lysine at position 93 of SEQ ID NO: 6, a asparagine at position 96 of SEQ ID NO: 6, a lysine at position 97 of SEQ ID NO: 6, an alanine at position 98 of SEQ ID NO: 6, and/or a histidine at position 207 of SEQ ID NO: 6.   
     
     
         52 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims comprising a variant IgG Fc polypeptide comprising:
 a) a tyrosine or a tryptophan at a position corresponding to position 138 of SEQ ID NO: 1, a tyrosine or a tryptophan at a position corresponding to position 137 of SEQ ID NO: 2, a tyrosine or a tryptophan at a position corresponding to position 137 of SEQ ID NO: 4, or a tyrosine or a tryptophan at a position corresponding to position 138 of SEQ ID NO: 6;   b) a tyrosine or a tryptophan at a position corresponding to position 154 of SEQ ID NO: 69, a tyrosine or a tryptophan at a position corresponding to position 154 of SEQ ID NO: 65 or SEQ ID NO: 66, or a tyrosine or a tryptophan at a position corresponding to position 154 of SEQ ID NO: 67 or SEQ ID NO: 68; or   c) a tyrosine or a tryptophan at a position corresponding to position 131 of SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56.   
     
     
         53 . A polypeptide comprising a variant IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises:
 a) a tyrosine or a tryptophan at a position corresponding to position 138 of SEQ ID NO: 1, a tyrosine or a tryptophan at a position corresponding to position 137 of SEQ ID NO: 2, a tyrosine or a tryptophan at a position corresponding to position 137 of SEQ ID NO: 4, or a tyrosine or a tryptophan at a position corresponding to position 138 of SEQ ID NO: 6;   b) a tyrosine or a tryptophan at a position corresponding to position 154 of SEQ ID NO: 69, a tyrosine or a tryptophan at a position corresponding to position 154 of SEQ ID NO: 65 or SEQ ID NO: 66, or a tyrosine or a tryptophan at a position corresponding to position 154 of SEQ ID NO: 67 or SEQ ID NO: 68; or   c) a tyrosine or a tryptophan at a position corresponding to position 131 of SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56.   
     
     
         54 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) a tyrosine or a tryptophan at position 138 of SEQ ID NO: 1, a tyrosine or a tryptophan at position 137 of SEQ ID NO: 2, a tyrosine or a tryptophan at position 137 of SEQ ID NO: 4, or a tyrosine or a tryptophan at position 138 of SEQ ID NO: 6; or   b) a tyrosine or a tryptophan at position 154 of SEQ ID NO: 69, a tyrosine or a tryptophan at position 154 of SEQ ID NO: 65 or SEQ ID NO: 66, or a tyrosine or a tryptophan at position 154 of SEQ ID NO: 67 or SEQ ID NO: 68; and/or   c) a tyrosine or a tryptophan at position 131 of SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56.   
     
     
         55 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims comprising a variant IgG Fc polypeptide comprising:
 a) a serine at a position corresponding to position 138 of SEQ ID NO: 1, a serine at a position corresponding to position 137 of SEQ ID NO: 2, a serine at a position corresponding to position 137 of SEQ ID NO: 4, a serine at a position corresponding to position 138 of SEQ ID NO: 6, a serine at a position corresponding to position 154 of SEQ ID NO: 69, a serine at a position corresponding to position 154 of SEQ ID NO: 65 or SEQ ID NO: 66, a serine at a position corresponding to position 154 of SEQ ID NO: 67 or SEQ ID NO: 68, or a serine at a position corresponding to position 131 of SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56;   b) an alanine at a position corresponding to position 140 of SEQ ID NO: 1, an alanine at a position corresponding to position 139 of SEQ ID NO: 2, an alanine at a position corresponding to position 139 of SEQ ID NO: 4, an alanine at a position corresponding to position 140 of SEQ ID NO: 6, an alanine at a position corresponding to position 156 of SEQ ID NO: 69, an alanine at a position corresponding to position 156 of SEQ ID NO: 65 or SEQ ID NO: 66, an alanine at a position corresponding to position 156 of SEQ ID NO: 67 or SEQ ID NO: 68, or an alanine at a position corresponding to position 133 of SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56; and/or   c) a threonine at a position corresponding to position 181 of SEQ ID NO: 1, a threonine at a position corresponding to position 180 of SEQ ID NO: 2, a threonine at a position corresponding to position 180 of SEQ ID NO: 4, a threonine at a position corresponding to position 181 of SEQ ID NO: 6, a threonine at a position corresponding to position 197 of SEQ ID NO: 69, a threonine at a position corresponding to position 197 of SEQ ID NO: 65 or SEQ ID NO: 66, a threonine at a position corresponding to position 197 of SEQ ID NO: 67 or SEQ ID NO: 68, or a threonine at a position corresponding to position 174 of SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56.   
     
     
         56 . A polypeptide comprising a variant IgG Fc polypeptide, wherein the variant IgG Fc polypeptide comprises:
 a) a serine at a position corresponding to position 138 of SEQ ID NO: 1, a serine at a position corresponding to position 137 of SEQ ID NO: 2, a serine at a position corresponding to position 137 of SEQ ID NO: 4, a serine at a position corresponding to position 138 of SEQ ID NO: 6, a serine at a position corresponding to position 154 of SEQ ID NO: 69, a serine at a position corresponding to position 154 of SEQ ID NO: 65 or SEQ ID NO: 66, a serine at a position corresponding to position 154 of SEQ ID NO: 67 or SEQ ID NO: 68, or a serine at a position corresponding to position 131 of SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56;   b) an alanine at a position corresponding to position 140 of SEQ ID NO: 1, an alanine at a position corresponding to position 139 of SEQ ID NO: 2, an alanine at a position corresponding to position 139 of SEQ ID NO: 4, an alanine at a position corresponding to position 140 of SEQ ID NO: 6, an alanine at a position corresponding to position 156 of SEQ ID NO: 69, an alanine at a position corresponding to position 156 of SEQ ID NO: 65 or SEQ ID NO: 66, an alanine at a position corresponding to position 156 of SEQ ID NO: 67 or SEQ ID NO: 68, or an alanine at a position corresponding to position 133 of SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56; and/or   c) a threonine at a position corresponding to position 181 of SEQ ID NO: 1, a threonine at a position corresponding to position 180 of SEQ ID NO: 2, a threonine at a position corresponding to position 180 of SEQ ID NO: 4, a threonine at a position corresponding to position 181 of SEQ ID NO: 6, a threonine at a position corresponding to position 197 of SEQ ID NO: 69, a threonine at a position corresponding to position 197 of SEQ ID NO: 65 or SEQ ID NO: 66, a threonine at a position corresponding to position 197 of SEQ ID NO: 67 or SEQ ID NO: 68, or a threonine at a position corresponding to position 174 of SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56.   
     
     
         57 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises:
 a) a serine at position 138 of SEQ ID NO: 1, a serine at position 137 of SEQ ID NO: 2, a serine at position 137 of SEQ ID NO: 4, a serine at position 138 of SEQ ID NO: 6, a serine at position 154 of SEQ ID NO: 69, a serine at position 154 of SEQ ID NO: 65 or SEQ ID NO: 66, a serine at position 154 of SEQ ID NO: 67 or SEQ ID NO: 68, or a serine at position 131 of SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56;   b) an alanine at position 140 of SEQ ID NO: 1, an alanine at position 139 of SEQ ID NO: 2, an alanine at position 139 of SEQ ID NO: 4, an alanine at position 140 of SEQ ID NO: 6, an alanine at position 156 of SEQ ID NO: 69, an alanine at position 156 of SEQ ID NO: 65 or SEQ ID NO: 66, an alanine at position 156 of SEQ ID NO: 67 or SEQ ID NO: 68, or an alanine at position 133 of SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56; and/or;   c) a threonine at position 181 of SEQ ID NO: 1, a threonine at position 181 of SEQ ID NO: 2, a threonine at position 181 of SEQ ID NO: 4, a threonine at position 181 of SEQ ID NO: 6, a threonine at position 197 of SEQ ID NO: 69, a threonine at position 197 of SEQ ID NO: 65 or SEQ ID NO: 66, a threonine at position 197 of SEQ ID NO: 67 or SEQ ID NO: 68, or a threonine at position 174 of SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56.   
     
     
         58 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the polypeptide or the variant Fc polypeptide is glycoslylated. 
     
     
         59 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the previous claims, wherein the polypeptide or the variant Fc polypeptide is aglycosylated. 
     
     
         60 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein L1 and L2, if present, each independently is a flexible linker. 
     
     
         61 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the amino acid sequence of L1 and L2, if present, each independently comprises 100%, at least 95%, at least 90%, at least 85% serine and/or glycine amino acid residues. 
     
     
         62 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the polypeptide, contiguous polypeptide, or multimeric polypeptide comprises an extension at a C-terminus. 
     
     
         63 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the polypeptide, contiguous polypeptide, or multimeric polypeptide comprises a glycine residue, two glycine residues, three glycine residues, four glycine residues, five glycine residues, six glycine residues, seven glycine residues, eight glycine residues, or greater than eight glycine residues at a C-terminus. 
     
     
         64 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the previous claims, wherein the contiguous polypeptide comprises an amino acid sequence of SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, or SEQ ID NO: 165 at its C-terminus. 
     
     
         65 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the therapeutic polypeptide, TPA1, and/or TPA2 is selected from an NGF polypeptide, a receptor of an NGF polypeptide (e.g., an ECD of a receptor of an NGF polypeptide), a TrkA polypeptide (e.g., an ECD of a TrkA polypeptide), an LNGFR polypeptide (e.g., an ECD of a LNGFR polypeptide), a TNFα polypeptide, a receptor of a TNFα polypeptide, a TNFR polypeptide (e.g., an ECD of a TNFR polypeptide), a TNFR1 polypeptide (e.g., an ECD of a TNFR1 polypeptide), a TNFR2 polypeptide (e.g., an ECD of a TNFR2 polypeptide), an IL5 polypeptide, a receptor of an IL5 polypeptide, an IL5R polypeptide (e.g., an ECD of an IL5R polypeptide), an IL5Rα polypeptide (e.g., an ECD of an IL5Rα polypeptide), an IL6 polypeptide, a receptor of an IL6 polypeptide, an IL6R polypeptide (e.g., an ECD of an IL6R polypeptide), an IL17 polypeptide, a receptor of an IL17 polypeptide, an IL17R polypeptide (e.g., an ECD of an IL17R polypeptide), an IL17RA polypeptide (e.g. an ECD of an IL17RA polypeptide), an IL17RB polypeptide (e.g., an ECD of an IL17RB polypeptide), an IL17RC polypeptide (e.g., an ECD of an IL17RC polypeptide), an IL23 polypeptide, a receptor of an IL23 polypeptide, an IL23R polypeptide (e.g., an ECD of an IL23R polypeptide), an IL12Rβ1 polypeptide (e.g., an ECD of an IL12β1 polypeptide), a PDL1 polypeptide, a receptor of a PDL1 polypeptide, a PDL2 polypeptide, a receptor of a PDL2 polypeptide, a PD1 polypeptide (e.g., an ECD of a PD1 polypeptide), an integrin polypeptide (e.g., ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGA10, ITGA11, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGA2B, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, or ITGB8 polypeptide), a receptor of an integrin polypeptide, a fibronectin polypeptide (e.g., an ECD of a fibronectin polypeptide), a vitronectin polypeptide (e.g., an ECD of a vitronectin polypeptide), a collagen polypeptide (e.g., an ECD of a collagen polypeptide), a laminin polypeptide (e.g., an ECD of a laminin polypeptide), a CD80 polypeptide, a receptor of a CD80 polypeptide, a CD86 polypeptide, a receptor of a CD86 polypeptide, a CTLA-4 polypeptide (e.g., an ECD of a CTLA-4 polypeptide), a B7-H3 polypeptide, a receptor of a B7-H3 polypeptide (e.g., an ECD of receptor of a B7-H3 polypeptide), a LAG-3 polypeptide (e.g., an ECD of a LAG-3 polypeptide), an IL31 polypeptide, a receptor of an IL31 polypeptide, an IL31RA polypeptide (e.g., an ECD of an IL31RA polypeptide), an OSMR polypeptide (e.g., an ECD of an OSMR polypeptide), an IL4 polypeptide, a receptor of an IL4R polypeptide, an IL4R polypeptide (e.g., an ECD of an IL4R polypeptide), an IL13 polypeptide, a receptor of an IL13 polypeptide, an IL13RA1 polypeptide (e.g., an ECD of an IL13RA1 polypeptide), an IL4R polypeptide (e.g., an ECD of an IL4R polypeptide), an IL13Rα2 polypeptide (e.g., an ECD of an IL13Rα2 polypeptide), an IL22 polypeptide, a receptor of an IL22 polypeptide (e.g., an ECD of an IL22 polypeptide), an IL22Rα1 polypeptide (e.g., an ECD of an IL22Rα1 polypeptide), an IL10Rβ2 polypeptide (e.g., an ECD of an IL10Rβ2 polypeptide), an IL33 polypeptide, a receptor of an IL33 polypeptide, an IL1RL1 polypeptide (e.g., an ECD of an IL1RL1 polypeptide), an EGF polypeptide, a receptor of an EGF polypeptide, a TGFα polypeptide, a receptor of a TGFα polypeptide, an EGFR polypeptide (e.g., an ECD of an EGFR polypeptide), an MMP9 polypeptide, an FGF polypeptide (e.g., FGF1, FGF2, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGF10, FGF11, FGF12, FGF13, FGF14, FGF15, FGF16, FGF17, FGF18, FGF19, FGF20, FGF21, FGF22, or FGF23 polypeptide), a receptor of an FGF polypeptide, an FGFR polypeptide (e.g., FGFR1, FGFR2, FGFR3, FGFR4, or FGFRL1 polypeptide), an ECD of an FGFR polypeptide (e.g., an ECD of an FGFR1, an FGFR2, an FGFR3, an FGFR4, or an FGFRL1 polypeptide), an EGF polypeptide, a receptor of an EGF polypeptide, a neuregulin polypeptide (e.g., a neuregulin isoform I, II, III, IV, V, or VI polypeptide), a receptor of a neuregulin polypeptide, a HER polypeptide (e.g., HER1, HER2, HER3, or HER4 polypeptide), an ECD of a HER polypeptide (e.g., an ECD of a HER1, a HER2, a HER3, or a HER4 polypeptide), an EpCAM polypeptide (e.g., an ECD of an EpCAM polypeptide), a CD20 polypeptide (e.g., an ECD of a CD20 polypeptide), a ligand of a CD20 polypeptide, a CD19 polypeptide (e.g., an ECD of a CD19 polypeptide), a ligand of a CD19 polypeptide, a CGRP polypeptide (e.g., an α-CGRP polypeptide or a β-CGRP polypeptide), a receptor of a CGRP polypeptide, a receptor of an α-CGRP polypeptide, a receptor of a β-CGRP polypeptide, a CALCRL polypeptide (e.g., an ECD of a CALCRL polypeptide), a RAMP polypeptide (e.g., RAMP1, RAMP2, or RAMP3 polypeptide), an ECD of a RAMP polypeptide (e.g., an ECD of a RAMP1, RAMP2, or RAMP3 polypeptide), an IGF polypeptide (e.g., an IGF-1 or an IGF-2 polypeptide), a receptor of an IGF polypeptide (e.g., a receptor of an IGF-1 or an IGF-2 polypeptide), an IGFR polypeptide (e.g., an IGFR1 or an IGFR2 polypeptide), an ECD of an IGFR polypeptide (e.g., an ECD of an IGFR1 or an IGFR2 polypeptide), an IGFBP polypeptide (e.g., IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, or IGFBP6 polypeptide), a VEGF polypeptide (e.g., VEGF-A, VEGF-B, VEGF-C, VEGF-D, or PGF polypeptide), a receptor of a VEGF polypeptide (e.g., a receptor of a VEGF-A, a VEGF-B, a VEGF-C, a VEGF-D, or a PGF polypeptide), a VEGFR polypeptide (e.g., a VEGFR1, a VEGFR2, or a VEGFR3 polypeptide), an ECD of a VEGFR polypeptide (e.g., an ECD of a VEGFR1, a VEGFR2, or a VEGFR3 polypeptide), an FLT1 receptor polypeptide (e.g., an ECD of an FLT1 receptor polypeptide), an IL36 polypeptide (e.g., IL36A, IL36B, or IL36G polypeptide), a receptor of an IL36 polypeptide (e.g., a receptor of an IL36A, an IL36B, or an IL36G polypeptide), an IL36R polypeptide (e.g., an ECD of an IL36R polypeptide), an IL1R1 polypeptide (e.g., an ECD of an IL1R1 polypeptide), an IL1R2 polypeptide (e.g., an ECD of an IL1R2 polypeptide), an IL1RL1 polypeptide (an ECD of an IL1RL1 polypeptide), an IL18R1 polypeptide (an ECD of an IL18R1 polypeptide), a bacterial toxin polypeptide, an exotoxin polypeptide, an endotoxin polypeptide, a Botulinum neurotoxin polypeptide, a Tetanus toxin polypeptide, a Staphylococcal toxin polypeptide, a CD52 polypeptide (e.g., an ECD of a CD52 polypeptide), a ligand of a CD52 polypeptide, a SIGLEC10 polypeptide, a PCSK9 polypeptide, a receptor of a PCSK9 polypeptide, an LDLR polypeptide (e.g., an ECD of an LDLR polypeptide), a CEA polypeptide (e.g., CD66a, CD66b, CD66c, CD66d, CD66e, or CD66f polypeptide), an ECD of a CEA polypeptide (e.g., an ECD of a CD66a, a CD66b, a CD66c, a CD66d, a CD66e, or a CD66f polypeptide), a BAFF polypeptide, a receptor of a BAFF polypeptide, a TRAF polypeptide (e.g., TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7 polypeptide), a receptor of a TRAF polypeptide (e.g., a receptor of a TRAF1, a TRAF2, a TRAF3, a TRAF4, a TRAF5 polypeptide), a BCMA polypeptide, an ECD of a BCMA polypeptide, a SOST polypeptide, a receptor of a SOST polypeptide, an LRP polypeptide (e.g., an LRP5 or an LRP6 polypeptide), an ECD of an LRP polypeptide (e.g., an ECD of an LRP5 or an LRP6 polypeptide), a DLL polypeptide (e.g., a DLL4 polypeptide), a receptor of a DLL polypeptide, a Jagged polypeptide (e.g., JAG1 or JAG polypeptide), a receptor of a Jagged polypeptide (e.g., a receptor of a JAG1 or a JAG polypeptide), a NOTCH polypeptide (e.g., NOTCH1, NOTCH2, NOTCH3, or NOTCH4 polypeptide), a ligand of a NOTCH polypeptide (e.g., a ligand of a NOTCH1, a NOTCH2, a NOTCH3, or a NOTCH4 polypeptide), a VWF polypeptide, a receptor of a VWF polypeptide, a Factor VIII polypeptide, a receptor of a Factor VIII polypeptide, a platelet GP1b receptor polypeptide (e.g., an ECD of a platelet GP1b receptor polypeptide), an integrin α IIb β 3  polypeptide (e.g., an ECD of an integrin α IIb β 3  polypeptide), an IL2 polypeptide, a receptor of an IL2 polypeptide, an IL2R polypeptide (e.g., an IL2Rα, an IL2Rβ, or an IL2Rγ polypeptide), an ECD of an IL2R polypeptide (e.g., an ECD of an IL2Rα, an IL2Rβ, or an IL2Rγ polypeptide), a TGFβ polypeptide, a receptor of a TGFβ polypeptide, a Decorin polypeptide, an EIF3I polypeptide, a LTBP1 polypeptide, a TGFβR1 polypeptide (e.g., an ECD of a TGFβR1 polypeptide), a YWHAE polypeptide, an IgE polypeptide, a receptor or an IgE polypeptide, an Fc receptor polypeptide (e.g., an FcεRI or an FcεRII polypeptide), an ECD of an Fc receptor polypeptide (e.g., an ECD of an FcεRI or an FcεRII polypeptide), a KLK polypeptide (e.g., KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14, or KLK15 polypeptide), a Rankl polypeptide, a receptor of a Rankl polypeptide, a RANK polypeptide (e.g., an ECD of a RANK polypeptide), a TSLP polypeptide, a receptor of a TSLP polypeptide, a CRLF2 polypeptide (e.g., an ECD of a CRLF2 polypeptide), an IL7Rα polypeptide (e.g., an ECD of an IL7Rα polypeptide), an S1P polypeptide, a CD3 polypeptide (e.g., a CD3γ polypeptide, a CD3δ polypeptide, or a CD3ε polypeptide), an ECD of a CD3 polypeptide (e.g., an ECD of a CD3γ polypeptide, a CD3δ polypeptide, or a CD3ε polypeptide), a CD80 polypeptide, a receptor of a CD80 polypeptide, a CD28 polypeptide (e.g., an ECD of a CD28 polypeptide), a CTLA-4 polypeptide (e.g., an ECD of a CTLA-4 polypeptide), a GnRH polypeptide, a receptor of a GNRH polypeptide, a GnRHR polypeptide (e.g., an ECD of a GnRHR polypeptide), an ICAM polypeptide (e.g., ICAM-1, ICAM-2, ICAM-3, ICAM-4, or ICAM-5 polypeptide), a receptor of an ICAM polypeptide (e.g., a receptor of an ICAM-1, an ICAM-2, an ICAM-3, an ICAM-4, or an ICAM-5 polypeptide), a JAM-A polypeptide, a receptor of a JAM-A polypeptide, an LFA-1 polypeptide (e.g., an ECD of an LFA-1 polypeptide), a Na v 1.7 polypeptide, a C5 polypeptide (e.g., a C5a or a C5b polypeptide), a receptor of a C5 polypeptide (e.g., a receptor of a C5a or a C5b polypeptide), a C5aR polypeptide (e.g., an ECD of a C5aR polypeptide), a C5L2 polypeptide (e.g., an ECD of a C5L2 polypeptide), an IL17 polypeptide, a receptor of an IL17 polypeptide, an IL17Ra polypeptide (e.g., an ECD of an IL17Ra polypeptide), an IL17RC polypeptide (e.g., an ECD of an IL17RC polypeptide), an EPO polypeptide, a somatostatin polypeptide, a GLP1 polypeptide, and a glucagon polypeptide. 
     
     
         66 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the therapeutic polypeptide, TPA1, and/or TPA2 is a canine polypeptide, a feline polypeptide, or an equine polypeptide. 
     
     
         67 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the antibody, TPA1, and/or TPA2 is an antibody that binds a target polypeptide selected from an NGF polypeptide, a receptor of an NGF polypeptide (e.g., an ECD of a receptor of an NGF polypeptide), a TrkA polypeptide (e.g., an ECD of a TrkA polypeptide), an LNGFR polypeptide (e.g., an ECD of a LNGFR polypeptide), a TNFα polypeptide, a receptor of a TNFα polypeptide, a TNFR polypeptide (e.g., an ECD of a TNFR polypeptide), a TNFR1 polypeptide (e.g., an ECD of a TNFR1 polypeptide), a TNFR2 polypeptide (e.g., an ECD of a TNFR2 polypeptide), an IL5 polypeptide, a receptor of an IL5 polypeptide, an IL5R polypeptide (e.g., an ECD of an IL5R polypeptide), an IL5Rα polypeptide (e.g., an ECD of an IL5Rα polypeptide), an IL6 polypeptide, a receptor of an IL6 polypeptide, an IL6R polypeptide (e.g., an ECD of an IL6R polypeptide), an IL17 polypeptide, a receptor of an IL17 polypeptide, an IL17R polypeptide (e.g., an ECD of an IL17R polypeptide), an IL17RA polypeptide (e.g. an ECD of an IL17RA polypeptide), an IL17RB polypeptide (e.g., an ECD of an IL17RB polypeptide), an IL17RC polypeptide (e.g., an ECD of an IL17RC polypeptide), an IL23 polypeptide, a receptor of an IL23 polypeptide, an IL23R polypeptide (e.g., an ECD of an IL23R polypeptide), an IL12Rβ1 polypeptide (e.g., an ECD of an IL12β1 polypeptide), a PDL1 polypeptide, a receptor of a PDL1 polypeptide, a PDL2 polypeptide, a receptor of a PDL2 polypeptide, a PD1 polypeptide (e.g., an ECD of a PD1 polypeptide), an integrin polypeptide (e.g., ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGA10, ITGA11, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGA2B, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, or ITGB8 polypeptide), a receptor of an integrin polypeptide, a fibronectin polypeptide (e.g., an ECD of a fibronectin polypeptide), a vitronectin polypeptide (e.g., an ECD of a vitronectin polypeptide), a collagen polypeptide (e.g., an ECD of a collagen polypeptide), a laminin polypeptide (e.g., an ECD of a laminin polypeptide), a CD80 polypeptide, a receptor of a CD80 polypeptide, a CD86 polypeptide, a receptor of a CD86 polypeptide, a CTLA-4 polypeptide (e.g., an ECD of a CTLA-4 polypeptide), a B7-H3 polypeptide, a receptor of a B7-H3 polypeptide (e.g., an ECD of receptor of a B7-H3 polypeptide), a LAG-3 polypeptide (e.g., an ECD of a LAG-3 polypeptide), an IL31 polypeptide, a receptor of an IL31 polypeptide, an IL31RA polypeptide (e.g., an ECD of an IL31RA polypeptide), an OSMR polypeptide (e.g., an ECD of an OSMR polypeptide), an IL4 polypeptide, a receptor of an IL4R polypeptide, an IL4R polypeptide (e.g., an ECD of an IL4R polypeptide), an IL13 polypeptide, a receptor of an IL13 polypeptide, an IL13RA1 polypeptide (e.g., an ECD of an IL13RA1 polypeptide), an IL4R polypeptide (e.g., an ECD of an IL4R polypeptide), an IL13Rα2 polypeptide (e.g., an ECD of an IL13Rα2 polypeptide), an IL22 polypeptide, a receptor of an IL22 polypeptide (e.g., an ECD of an IL22 polypeptide), an IL22Rα1 polypeptide (e.g., an ECD of an IL22Rα1 polypeptide), an IL10Rβ2 polypeptide (e.g., an ECD of an IL10Rβ2 polypeptide), an IL33 polypeptide, a receptor of an IL33 polypeptide, an IL1RL1 polypeptide (e.g., an ED of an IL1RL1 polypeptide), an EGF polypeptide, a receptor of an EGF polypeptide, a TGFα polypeptide, a receptor of a TGFα polypeptide, an EGFR polypeptide (e.g., an ECD of an EGFR polypeptide), an MMP9 polypeptide, an FGF polypeptide (e.g., FGF1, FGF2, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGF10, FGF11, FGF12, FGF13, FGF14, FGF15, FGF16, FGF17, FGF18, FGF19, FGF20, FGF21, FGF22, or FGF23 polypeptide), a receptor of an FGF polypeptide, an FGFR polypeptide (e.g., FGFR1, FGFR2, FGFR3, FGFR4, or FGFRL1 polypeptide), an ECD of an FGFR polypeptide (e.g., an ECD of an FGFR1, an FGFR2, an FGFR3, an FGFR4, or an FGFRL1 polypeptide), an EGF polypeptide, a receptor of an EGF polypeptide, a neuregulin polypeptide (e.g., a neuregulin isoform I, II, III, IV, V, or VI polypeptide), a receptor of a neuregulin polypeptide, a HER polypeptide (e.g., HER1, HER2, HER3, or HER4 polypeptide), an ECD of a HER polypeptide (e.g., an ECD of a HER1, a HER2, a HER3, or a HER4 polypeptide), an EpCAM polypeptide (e.g., an ECD of an EpCAM polypeptide), a CD20 polypeptide (e.g., an ECD of a CD20 polypeptide), a ligand of a CD20 polypeptide, a CD19 polypeptide (e.g., an ECD of a CD19 polypeptide), a ligand of a CD19 polypeptide, a CGRP polypeptide (e.g., an α-CGRP polypeptide or a β-CGRP polypeptide), a receptor of a CGRP polypeptide, a receptor of an α-CGRP polypeptide, a receptor of a β-CGRP polypeptide, a CALCRL polypeptide (e.g., an ECD of a CALCRL polypeptide), a RAMP polypeptide (e.g., RAMP1, RAMP2, or RAMP3 polypeptide), an ECD of a RAMP polypeptide (e.g., an ECD of a RAMP1, RAMP2, or RAMP3 polypeptide), an IGF polypeptide (e.g., an IGF-1 or an IGF-2 polypeptide), a receptor of an IGF polypeptide (e.g., a receptor of an IGF-1 or an IGF-2 polypeptide), an IGFR polypeptide (e.g., an IGFR1 or an IGFR2 polypeptide), an ECD of an IGFR polypeptide (e.g., an ECD of an IGFR1 or an IGFR2 polypeptide), an IGFBP polypeptide (e.g., IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, or IGFBP6 polypeptide), a VEGF polypeptide (e.g., VEGF-A, VEGF-B, VEGF-C, VEGF-D, or PGF polypeptide), a receptor of a VEGF polypeptide (e.g., a receptor of a VEGF-A, a VEGF-B, a VEGF-C, a VEGF-D, or a PGF polypeptide), a VEGFR polypeptide (e.g., a VEGFR1, a VEGFR2, or a VEGFR3 polypeptide), an ECD of a VEGFR polypeptide (e.g., an ECD of a VEGFR1, a VEGFR2, or a VEGFR3 polypeptide), an FLT1 receptor polypeptide (e.g., an ECD of an FLT1 receptor polypeptide), an IL36 polypeptide (e.g., IL36A, IL36B, or IL36G polypeptide), a receptor of an IL36 polypeptide (e.g., a receptor of an IL36A, an IL36B, or an IL36G polypeptide), an IL36R polypeptide (e.g., an ECD of an IL36R polypeptide), an IL1R1 polypeptide (e.g., an ECD of an IL1R1 polypeptide), an IL1R2 polypeptide (e.g., an ECD of an IL1R2 polypeptide), an IL1RL1 polypeptide (an ECD of an IL1RL1 polypeptide), an IL18R1 polypeptide (an ECD of an IL18R1 polypeptide), a bacterial toxin polypeptide, an exotoxin polypeptide, an endotoxin polypeptide, a Botulinum neurotoxin polypeptide, a Tetanus toxin polypeptide, a Staphylococcal toxin polypeptide, a CD52 polypeptide (e.g., an ECD of a CD52 polypeptide), a ligand of a CD52 polypeptide, a SIGLEC10 polypeptide, a PCSK9 polypeptide, a receptor of a PCSK9 polypeptide, an LDLR polypeptide (e.g., an ECD of an LDLR polypeptide), a CEA polypeptide (e.g., CD66a, CD66b, CD66c, CD66d, CD66e, or CD66f polypeptide), an ECD of a CEA polypeptide (e.g., an ECD of a CD66a, a CD66b, a CD66c, a CD66d, a CD66e, or a CD66f polypeptide), a BAFF polypeptide, a receptor of a BAFF polypeptide, a TRAF polypeptide (e.g., TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7 polypeptide), a receptor of a TRAF polypeptide (e.g., a receptor of a TRAF1, a TRAF2, a TRAF3, a TRAF4, a TRAF5 polypeptide), a BCMA polypeptide, an ECD of a BCMA polypeptide, a SOST polypeptide, a receptor of a SOST polypeptide, an LRP polypeptide (e.g., an LRP5 or an LRP6 polypeptide), an ECD of an LRP polypeptide (e.g., an ECD of an LRP5 or an LRP6 polypeptide), a DLL polypeptide (e.g., a DLL4 polypeptide), a receptor of a DLL polypeptide, a Jagged polypeptide (e.g., JAG1 or JAG polypeptide), a receptor of a Jagged polypeptide (e.g., a receptor of a JAG1 or a JAG polypeptide), a NOTCH polypeptide (e.g., NOTCH1, NOTCH2, NOTCH3, or NOTCH4 polypeptide), a ligand of a NOTCH polypeptide (e.g., a ligand of a NOTCH1, a NOTCH2, a NOTCH3, or a NOTCH4 polypeptide), a VWF polypeptide, a receptor of a VWF polypeptide, a Factor VIII polypeptide, a receptor of a Factor VIII polypeptide, a platelet GP1b receptor polypeptide (e.g., an ECD of a platelet GP1b receptor polypeptide), an integrin α IIb β 3  polypeptide (e.g., an ECD of an integrin α IIb β 3  polypeptide), an IL2 polypeptide, a receptor of an IL2 polypeptide, an IL2R polypeptide (e.g., an IL2Rα, an IL2Rβ, or an IL2Rγ polypeptide), an ECD of an IL2R polypeptide (e.g., an ECD of an IL2Rα, an IL2Rβ, or an IL2Rγ polypeptide), a TGFβ polypeptide, a receptor of a TGFβ polypeptide, a Decorin polypeptide, an EIF3I polypeptide, a LTBP1 polypeptide, a TGFβR1 polypeptide (e.g., an ECD of a TGFβR1 polypeptide), a YWHAE polypeptide, an IgE polypeptide, a receptor or an IgE polypeptide, an Fc receptor polypeptide (e.g., an FcεRI or an FcεRII polypeptide), an ECD of an Fc receptor polypeptide (e.g., an ECD of an FcεRI or an FcεRII polypeptide), a KLK polypeptide (e.g., KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14, or KLK15 polypeptide), a Rankl polypeptide, a receptor of a Rankl polypeptide, a RANK polypeptide (e.g., an ECD of a RANK polypeptide), a TSLP polypeptide, a receptor of a TSLP polypeptide, a CRLF2 polypeptide (e.g., an ECD of a CRLF2 polypeptide), an IL7Rα polypeptide (e.g., an ECD of an IL7Rα polypeptide), an S1P polypeptide, a CD3 polypeptide (e.g., a CD3γ polypeptide, a CD3δ polypeptide, or a CD3ε polypeptide), an ECD of a CD3 polypeptide (e.g., an ECD of a CD3γ polypeptide, a CD3δ polypeptide, or a CD3ε polypeptide), a CD80 polypeptide, a receptor of a CD80 polypeptide, a CD28 polypeptide (e.g., an ECD of a CD28 polypeptide), a CTLA-4 polypeptide (e.g., an ECD of a CTLA-4 polypeptide), a GnRH polypeptide, a receptor of a GNRH polypeptide, a GnRHR polypeptide (e.g., an ECD of a GnRHR polypeptide), an ICAM polypeptide (e.g., ICAM-1, ICAM-2, ICAM-3, ICAM-4, or ICAM-5 polypeptide), a receptor of an ICAM polypeptide (e.g., a receptor of an ICAM-1, an ICAM-2, an ICAM-3, an ICAM-4, or an ICAM-5 polypeptide), a JAM-A polypeptide, a receptor of a JAM-A polypeptide, an LFA-1 polypeptide (e.g., an ECD of an LFA-1 polypeptide), a Na v 1.7 polypeptide, a C5 polypeptide (e.g., a C5a or a C5b polypeptide), a receptor of a C5 polypeptide (e.g., a receptor of a C5a or a C5b polypeptide), a C5aR polypeptide (e.g., an ECD of a C5aR polypeptide), a C5L2 polypeptide (e.g., an ECD of a C5L2 polypeptide), an IL17 polypeptide, a receptor of an IL17 polypeptide, an IL17Ra polypeptide (e.g., an ECD of an IL17Ra polypeptide), an IL17RC polypeptide (e.g., an ECD of an IL17RC polypeptide), an EPO polypeptide, a somatostatin polypeptide, a GLP1 polypeptide, and a glucagon polypeptide. 
     
     
         68 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the antibody binds a canine target polypeptide, a feline target polypeptide, or an equine target polypeptide. 
     
     
         69 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims, wherein the variant IgG Fc polypeptide comprises an amino acid sequence having at least 90% identity, at least 95% identity, at least 97% identity, or at least 99% identity to the amino acid sequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, and/or 250. 
     
     
         70 . The polypeptide, the contiguous polypeptide, or the multimeric protein of any one of the preceding claims comprising an amino acid sequence of SEQ ID NO: 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 57, 58, 59, 60, 61, 62, 63, 64, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 146, 147, 148, 149, 150, 151, 154, 155, 157, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 271, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, and/or 250. 
     
     
         71 . A polypeptide comprising an amino acid sequence of SEQ ID NO: 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 57, 58, 59, 60, 61, 62, 63, 64, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 146, 147, 148, 149, 150, 151, 154, 155, 157, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 271, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, and/or 250. 
     
     
         72 . The polypeptide, the multimeric protein, or the contiguous polypeptide of any one of the preceding claims, wherein the at least one amino acid modification or substitution comprises an amino acid substitution with an amino acid derivative. 
     
     
         73 . An isolated nucleic acid encoding the polypeptide, the multimeric protein, or the contiguous polypeptide of any one of the preceding claims. 
     
     
         74 . A host cell comprising the nucleic acid of  claim 73 . 
     
     
         75 . A method of producing a polypeptide comprising culturing the host cell of  claim 74  and isolating the polypeptide. 
     
     
         76 . A pharmaceutical composition comprising the polypeptide, the multimeric protein, or the contiguous polypeptide of any one of  claims 1  to  72 , and a pharmaceutically acceptable carrier. 
     
     
         77 . A method of exposing a cell to the polypeptide, the multimeric protein, the contiguous polypeptide, or the pharmaceutical composition of any one of  claim 1  to  72  or  76 . 
     
     
         78 . The method of  claim 77 , wherein the cell is exposed to the polypeptide, heterodimeric protein, contiguous polypeptide, or the pharmaceutical composition ex vivo. 
     
     
         79 . The method of  claim 77 , wherein the cell is exposed to the polypeptide, heterodimeric protein, contiguous polypeptide, or the pharmaceutical composition in vivo. 
     
     
         80 . The method of any one of  claims 77  to  79 , wherein the cell is a human cell, a canine cell, a feline cell, or an equine cell. 
     
     
         81 . A method of delivering a polypeptide to a subject comprising administering the polypeptide, the multimeric protein, the contiguous polypeptide, or the pharmaceutical composition of any one of  claim 1  to  72  or  76  parenterally. 
     
     
         82 . A method of delivering a polypeptide to a subject comprising administering the polypeptide, the multimeric protein, the contiguous polypeptide, or the pharmaceutical composition of any one of  claim 1  to  72  or  76  by an intramuscular route, an intraperitoneal route, an intracerebrospinal route, a subcutaneous route, an intra-arterial route, an intrasynovial route, an intrathecal route, or an inhalation route. 
     
     
         83 . A method of treating a subject having diabetes or obesity, the method comprising administering to the subject a therapeutically effective amount of the polypeptide, the multimeric protein, the contiguous polypeptide, or the pharmaceutical composition of any one of  claim 1  to  72  or  76 . 
     
     
         84 . The method of any one of  claims 81  to  83 , wherein the subject is a human subject. 
     
     
         85 . The method of any one of  claims 81  to  83 , wherein the subject is a companion animal species. 
     
     
         86 . The method of  claim 85 , wherein the companion animal species is canine, equine, or feline.